[The Application Study of Voriconazole and Its Metabolites Concentration Monitoring in Allogeneic Hematopoietic Stem...

To explore the application value of simultaneous monitoring of voriconazole (VRCZ) and voriconazole N-oxide (VNO) in efficacy and safety of VRCZ in the prevention and treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients before engraftment (i.e., days +1 to +30 after transplantation).

The influencing factors of VRCZ, VNO concentration and MR (C_VNO/C_VRCZ) and the difference of VRCZ in the prevention and treatment of fungal infection and liver and kidney injury were analyzed. The receiver operating characteristic curve (ROC) was used to analyze the differences (the corresponding to the maximum of the Youden index on the curve was set as the cut-off value) to confirm the critical value.

The factors affecting VRCZ concentration (C_VRCZ), VNO concentration (C_VNO) and MR were patient weight, VRCZ daily dose, and transplantation type (all P < 0.05). C_VRCZ and C_VNO in the effective group were higher than those in the ineffective group (P < 0.001), the opposite of MR (P < 0.001); the liver and renal injury group had lower MR than the normal group (P < 0.05). ROC showed that C_VRCZ, C _VNO and MR had important value in predicting VRCZ in the prevention and treatment of invasive fungal infections in allo-HSCT patients before engraftment, and their cutoff of concentrations were 0.95 μg/ml, 1.35 μg/ml and 1.645, respectively (AUC: 0.9677, 0.7634, 0.9564). C_VRCZ and MR can assist in indicating liver ［cutoff values: 0.65 μg/ml, 1.96 (AUC: 0.5971, 0.6663)］ and renal injury ［cutoff values: 0.95 μg/ml, 1.705 (AUC: 0.6039, 0.6164)］.

The great value of simultaneous monitoring of VRCZ, VNO and MR can predict in the efficacy and safety of VRCZ in allo-HSCT patients before engraftment. The prediction accuracy of C_VRCZ was higher than that of MR, followed by that of C_VNO. Increased C_VRCZ and decreased MR increase the risk of liver and kidney injury.